Visit Dr. Gendelman's Lab
HOWARD E. GENDELMAN MD
Margaret R. Larson Professor of Internal Medicine and Infectious Diseases
Chair, Department of Pharmacology and Experimental Neuroscience
Durham Research Center, 8008
985880 Nebraska Medical Center
Omaha, NE 68198-5880
In the news:
UNMC Today, April 24, 2014
Outstanding Faculty Mentor of Graduate Students: Howard Gendelman, M.D.
KETV.com, January 10, 2014
UNMC researches test vaccine for Parkinson's disease
UNMC Newsroom, October 14, 2013
Dr. Gendelman named "Innovator of the Year"
UNMC Today, July 10, 2013
Investigators to Launch Clinical Trial Testing Parkinson's Therapy
Omaha World-Herald, Live Well, July 1, 2013
One-two punch vs. Parkinson's: meds and a machine
Dr. Howard E. Gendelman is the Margaret R. Larson Professor of Internal Medicine and Infectious Diseases, Chairman of the Department of Pharmacology and Experimental Neuroscience, and Director of the Center for Neurodegenerative Disorders at the University of Nebraska Medical Center. Dr. Gendelman is credited in unraveling how functional alterations in brain immunity induce metabolic changes and ultimately lead to neural cell damage for a broad range of infectious, metabolic and neurodegenerative disorders. These discoveries have had broad implications in developmental therapeutics aimed at preventing, slowing or reversing neural maladies. He is also credited for the demonstration that AIDS dementia is a reversible metabolic encephalopathy; a finding realized at the University of Nebraska Medical Center. His work has led to novel immunotherapy and nanomedicine strategies for Parkinson’s and viral diseases currently being tested in early clinical trials as a result of intense translational investigations.
Dr. Gendelman obtained a Bachelor’s degree in Natural Sciences and Russian Studies with honors from Muhlenberg College and his M.D. from the Pennsylvania State University-Hershey Medical Center where he was the 1999 Distinguished Alumnus. He completed a residency in Internal medicine at Montefiore Hospital, Albert Einstein College of Medicine and was a Clinical and Research Fellow in Neurology and Infectious Diseases at the Johns Hopkins University Medical Center. He occupied senior faculty and research positions at the Johns Hopkins Medical Institutions, the National Institute of Allergy and Infectious Diseases, the Uniformed Services University of the Health Sciences Center, the Walter Reed Army Institute of Research, and the Henry Jackson Foundation for the Advancement in Military Medicine before joining the University of Nebraska Medical Center faculty in March of 1993. He retired from the US Army with the rank of Lieutenant Colonel. Dr. Gendelman has authored over 400 peer-reviewed publications, edited nine books and monographs, holds eight patents, is the Editor-In-Chief and Founder of the Journal of Neuroimmune Pharmacology along with service on numerous editorial boards, national and international scientific review and federal and state committees. He has been an invited lecturer to more than 200 scientific seminars and symposia and the recipient of numerous local, national and international honors. These, include, but are not limited to, the Henry L. Moses Award in Basic Science; the Carter-Wallace Fellow for Distinction in AIDS Research, the David T. Purtilo Distinguished Chair of Pathology and Microbiology, the UNMC Scientist Laureate; NU Outstanding Research and Creativity and the Joseph Wybran Distinguished Scientist Awards. Dr. Gendelman was named a J. William Fulbright Research Scholar at the Weizmann Institute of Science in Israel. In 2001, he received the prestigious Jacob Javits Neuroscience Research Award and the Career Research Award in Medicine from UNMC.
He is included amongst a selective scientific group listed on highly cited.com as one of the top cited scientists in his field. Dr. Gendelman has trained more than forty scientists (students and postdoctoral fellows) who have themselves developed independent successful careers. Under his leadership, the department now holds scores of independent R01s or equivalent grants, four program project grants, and shares two program developmental awards. His leadership is credited with the growth of the Department of Pharmacology and Experimental Neuroscience at the University of Nebraska Medical Center to be amongst the top-like ranked and federally funded departments (top ten) nationwide; a particularly noted feat as its position was 77 when he assumed its leadership.
The neuroregeneration laboratory provides the student or postdoctoral fellow with broad research experiences in diagnostics, pathogenic mechanisms and therapies for neurodegenerative disorders.
The major focus for our research is on the role played by glial inflammatory activities in brain disease. The work bridges immunology, neuroscience and pharmacology and crosses disease barriers for studies of HIV-1-associated neurocognitive disorders, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). The major goal is to use immune-based approaches to reverse nerve cell damage.
The laboratory initiative is divided into specific programs with cross-disciplinary support provided through experienced senior scientists. Specific expertise is available in proteomics, immunology, molecular neuroscience, infectious disease, neurophysiology and neuropathogenesis.
Research priorities in nanomedicine focuses on drug delivery to the central nervous system using "smart" drugs that are packaged into immunocytes and use “Trojan horse” cell-based mechanisms to by-pass the blood-brain barrier and enter diseased brain areas. These are intertwined with studies of disease pathogenesis focused on studies of the biophysical and effector cell properties of blood-borne macrophages that modulate leukocyte entry and glial immunity.
Our nanomedicine program provides laboratory experiences in nanoformulations and physical chemistry linked to characterization of nanoparticles as well as animal studies of disease pathobiology using "state of the art" drug delivery systems. Coordinate drug testing (anti-inflammatory, neuroprotective and anti-retroviral) in HIV-1 encephalitis (HIVE) and PD are pursued with adjunctive drugs distinct or part of the nanomedicine efforts.
This program is part of multiple National Institutes of Health grant efforts that involve scientists at the University of Nebraska Medical Center (College of Medicine and College of Pharmacy), the University of Rochester, and Columbia University College of Physicians and Surgeons. The focus is to perform translational research that would move quickly from animals to humans and currently involves human phase I testings.
Our neuroimmunologic and vaccine approaches have shown tremendous success in recent years for their abilities to induce protective immunity and protect against ongoing neurodegeneration. These are being pursued in animal models of HIVE, PD and ALS.
Our proteomic and metabolomic studies involve basic cell biology and molecular studies of virus-cell interactions in the setting of abused drugs.
All together this is a rich offering in scientific disciplines and relevant human disease models that can readily translate from the laboratory bench to the clinic.
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Representative Publications (H index 80):
- Nell A, Swindells S, Bronich T, Gendelman HE. Interview: Nanomedicine and the fight against HIV/AIDS. Nanomedicine (London, England). 2014; Vol. 9: p. 1-14. 1743-5889. PMID 24552561
- Gendelman, HE, Mosley, RL, Boska MD, McMillan J. The promise of nanoneuromedicine. Nanomedicine. 9 : 171-176. 2014. PMID: 24552556
- Martinez-Skinner AL, Veerubhotla RS, Liu H, Xiong H, Yu F, McMillan JM, Gendelman HE (2013). Functional proteome of macrophage carried nanoformulated antiretroviral therapy demonstrates enhanced particle carrying capacity. J Proteome Res. 12(5):2282-94. PMID 23544708
- Nowacek A, Kadiu I, McMillan J, Gendelman HE (2013). Immunoisolation of nanoparticles containing endocytic vesicles for drug quantitation. Methods Mol Biol. 991:41-6. PMID 23546657
- Nowacek A, Kadiu I, McMillan J, Gendelman HE (2013). Methods for isolation and identification of nanoparticle-containing subcellular compartments. Methods Mol Biol. 991:47-55. PMID 23546658
- Ma Q, Gelbard HA, Maggirwar SB, Dewhurst S, Gendelman HE, Peterson DR, Difrancesco R, Hochreiter JS, Morse GD, Schifitto G (2013). Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients. J Neurovirol. 19(3):254-60. PMID 23737347
- Gautam N, Roy U, Balkundi S, Puligujja P, Guo D, Smith N, Liu XM, Lamberty B, Morsey B, Fox HS, McMillan J, Gendelman HE, Alnouti Y (2013). Preclinical pharmacokinetics and tissue distribution of long-acting nanoformulated antiretroviral therapy. Antimicrob Agents Chemother. 57(7):3110-20. PMID 23612193
- Liu Y, Sajja BR, Gendelman HE, Boska MD. Mouse brain fixation to preserve In vivo manganese enhancement for ex vivo manganese-enhanced MRI. J Magn Reson Imaging. 38(2):482-7. PMID 23349027
- Williams J, Sayles HR, Meza JL, Sayre P, Sandkovsky U, Gendelman HE, Flexner C, Swindells S. Long-acting parenteral nanoformulated antiretroviral therapy: interest and attitudes of HIV-infected patients. Nanomedicine (Lond). 8(11):1807-13. PMID 23611617
- Haney MJ, Zhao Y, Harrison EB, Mahajan V, Ahmed S, He Z, Suresh P, Hingtgen SD, Klyachko NL, Mosley RL, Gendelman HE, Kabanov AV, Batrakova EV. (2013) Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases. PLoS One 8(4):e61852. PMID 23620794
- Guo D, Li T, McMillan J, Sajja BR, Puligujja P, Boska MD, Gendelman HE, Liu XM (in press, 2013). Small magnetite antiretroviral therapeutic nanoparticle probes for MRI of drug biodistribution. Nanomedicine (Lond) August 2013. PMID 23905578
- Bade AN, Zhou B, Epstein AA, Gorantla S, Poluektova LY, Luo J, Gendelman HE, Boska MD, Liu Y. Improved Visualization of Neuronal Injury Following Glial Activation by Manganese Enhanced MRI. J Neuroimmune Pharmacol. 8(4):1027-36. PMID 23729245
- Epstein AA, Narayanasamy P, Dash PK, High R, Bathena SP, Gorantla S, Poluektova LY, Alnouti Y, Gendelman HE, Boska MD. Combinatorial assessments of brain tissue metabolomics and histopathology in rodent models of human immunodeficiency virus infection. J Neuroimmune Pharmacol. 8(5):1224-38. PMID 23702663
- Puligujja P, McMillan J, Kendrick L, Li T, Balkundi S, Smith N, Veerubhotla RS, Edagwa BJ, Kabanov AV, Bronich T, Gendelman HE, Liu XM. Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections. Nanomedicine. 9(8):1263-73. PMID 23680933
- Roy U, McMillan J, Alnouti Y, Gautum N, Smith N, Balkundi S, Dash P, Gorantla S, Martinez-Skinner A, Meza J, Kanmogne G, Swindells S, Cohen SM, Mosley RL, Poluektova L, Gendelman HE. Pharmacodynamic and Antiretroviral Activities of Combination Nanoformulated Antiretrovirals in HIV-1-Infected Human PBL-Reconstituted Mice. J Infect Dis, 2012. Nov 15;206(10):1577-88. PMID: 22811299
- Dash, P., Gendelman, H.E., Roy, U., Balkundi, S., Alnouti, Y., Mosley, R.L., Gelbard, H.A., McMillan, J., Gorantla, S., Poluektova, L. Long-Acting NanoART Elicits Potent Antiretroviral and Neuroprotective Responses in HIV-1 Infected Humanized Mice. AIDS, 2012.Nov 13;26(17):2135-44. PMID 22824628
- Kanmogne, G.D., Singh, S., Roy, U., Liu, X., McMillan, J., Gorantla, S., Balkundi, S., Smith, N., Alnouti, Y., Gautam, N., Zhou, Y., Poluektova, L., Kabanov, A., Bronich, T., Gendelman, H.E. Mononuclear Phagocyte Intercellular Crosstalk Facilitates Transmission of Cell Targeted Nanoformulated Antiretroviral Drugs to Human Brain Endothelial Cells., Intl J Nanomedicine, 2012:7;2373-2388. PMID 22661891
- Zhao Y, Haney MJ, Klyachko NL, Li S, Booth SL, Higginbotham SM, Jones J, Zimmerman MC, Mosley RL, Kabanov AV, Gendelman HE, Batrakova EV. Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles. Nanomedicine (Lond). 2011 Jan;6(1):25-42. PMID 21182416
- Boska M, Liu Y, Uberti M, Sajja BR, Balkundi S, McMillan J, Gendelman HE. Registered bioimaging of nanomaterials for diagnostic and therapeutic monitoring. J Vis Exp. 2010 Dec 9;(46). PMID 21178969
- Balkundi S, Nowacek AS, Roy U, Martinez-Skinner A, McMillan J, Gendelman HE. Methods development for blood borne macrophage carriage of nanoformulated antiretroviral drugs. J Vis Exp. 2010 Dec 9;(46). PMID 21178968
- Bressani RF, Nowacek AS, Singh S, Balkundi S, Rabinow B, McMillan J, Gendelman HE, Kanmogne GD. Pharmacotoxicology of monocyte-macrophage nanoformulated antiretroviral drug uptake and carriage. Nanotoxicology. 2011 Dec; 5(4):592-605. PMID 21175298
- Kraft-Terry S, Gerena Y, Wojna V, Plaud-Valentin M, Rodriguez Y, Ciborowski P, Mayo R, Skolasky R, Gendelman HE, Meléndez LM. Proteomic analyses of monocytes obtained from Hispanic women with HIV-associated dementia show depressed antioxidants. Proteomics Clin Appl. 2010 Sep;4(8-9):706-14. PMID 21137088
- Nowacek AS, Balkundi S, McMillan J, Roy U, Martinez-Skinner A, Mosley RL, Kanmogne G, Kabanov AV, Bronich T, Gendelman HE. Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages. J Control Release. 2011 Mar 10; 150(2):204-11. PMID 21108978
- Gorantla S, Makarov E, Finke-Dwyer J, Castanedo A, Holguin A, Gebhart CL, Gendelman HE, Poluektova L. Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis. Am J Pathol. 2010 Dec;177(6):2938-49. PMID 21088215
- Huang X, Stone DK, Yu F, Zeng Y, Gendelman HE. Functional proteomic analysis for regulatory T cell surveillance of the HIV-1-infected macrophage. J Proteome Res. 2010 Dec 3;9(12):6759-73. PMID 20954747
- Gelbard HA, Dewhurst S, Maggirwar SB, Kiebala M, Polesskaya O, Gendelman HE. Rebuilding synaptic architecture in HIV-1 associated neurocognitive disease: a therapeutic strategy based on modulation of mixed lineage kinase. Neurotherapeutics. 2010 Oct;7(4):392-8. PMID 20880503
- Gong N, Liu J, Reynolds AD, Gorantla S, Mosley RL, Gendelman HE. Brain ingress of regulatory T cells in a murine model of HIV-1 encephalitis. J Neuroimmunol. 2011 Jan; 230 (1-2):33-41. PMID 20846730
- Wiederin JL, Donahoe RM, Anderson JR, Yu F, Fox HS, Gendelman HE, Ciborowski PS. Plasma proteomic analysis of simian immunodeficiency virus infection of rhesus macaques. J Proteome Res. 2010 Sep 3;9(9):4721-31. PMID 20677826
- Gorantla S, Makarov E, Roy D, Finke-Dwyer J, Murrin LC, Gendelman HE, Poluektova L. Immunoregulation of a CB2 receptor agonist in a murine model of neuroAIDS. J Neuroimmune Pharmacol. 2010 Sep;5(3):456-68. PMID 20549374
- Kosloski LM, Ha DM, Hutter JA, Stone DK, Pichler MR, Reynolds AD, Gendelman HE, Mosley RL. Adaptive immune regulation of glial homeostasis as an immunization strategy for neurodegenerative diseases. J Neurochem. 2010 Sep 1;114(5):1261-76. PMID 20524958
- Gorantla S, Makarov E, Finke-Dwyer J, Gebhart CL, Domm W, Dewhurst S, Gendelman HE, Poluektova LY. CD8+ cell depletion accelerates HIV-1 immunopathology in humanized mice. J Immunol. 2010 Jun 15;184(12):7082-91. PMID 20495069
- Brynskikh AM, Zhao Y, Mosley RL, Li S, Boska MD, Klyachko NL, Kabanov AV, Gendelman HE, Batrakova EV. Macrophage delivery of therapeutic nanozymes in a murine model of Parkinson's disease. Nanomedicine (Lond). 2010 Apr;5(3):379-96. PMID 20394532
- Kiyota T, Okuyama S, Swan RJ, Jacobsen MT, Gendelman HE, Ikezu T. CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer's disease-like pathogenesis in APP+PS1 bigenic mice. FASEB J. 2010 Aug;24(8):3093-102. PMID 20371618
- Yao H, Yang Y, Kim KJ, Bethel-Brown C, Gong N, Funa K, Gendelman HE, Su TP, Wang JQ, Buch S. Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration. Blood. 2010 Jun 10;115(23):4951-62. PMID 20354174
- Nowacek AS, McMillan J, Miller R, Anderson A, Rabinow B, Gendelman HE. Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: implications for neuroAIDS therapeutics. J Neuroimmune Pharmacol. 2010 Dec;5(4):592-601. PMID 20237859
- Reynolds AD, Stone DK, Hutter JA, Benner EJ, Mosley RL, Gendelman HE. Regulatory T cells attenuate Th17 cell-mediated nigrostriatal dopaminergic neurodegeneration in a model of Parkinson's disease. J Immunol. 2010 Mar 1;184(5):2261-71. PMID 20118279
- Batrakova EV, Li S, Brynskikh AM, Sharma AK, Li Y, Boska M, Gong N, Mosley RL, Alakhov VY, Gendelman HE, Kabanov AV. Effects of pluronic and doxorubicin on drug uptake, cellular metabolism, apoptosis and tumor inhibition in animal models of MDR cancers. J Control Release. 2010 May 10;143(3):290-301. PMID 20074598
- Gendelman HE, Ding S, Gong N, Liu J, Ramirez SH, Persidsky Y, Mosley RL, Wang T, Volsky DJ, Xiong H. Monocyte Chemotactic Protein-1 Regulates Voltage-Gated K(+) Channels and Macrophage Transmigration. J Neuroimmune Pharmacol. 4(1):47-59 2009. PMID 19034671
- Dou H, Grotepas CB, Zeng C, Destache CJ, Shlyakhtenko L, Chaubal M, Werling J, Kipp J, Rabinow BE, Gendelman HE. Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of NeuroAIDS. J. Immunol. Jul 1;183(1):661-9 2009. PMID 19535632
- Beduneau A, Grotepas CB, Kabanov A, Rabinow BE, Gong N, Mosely RL, Boska MD, Dou H, Gendelman HE. Facilitated monocyte-macrophage uptake and tissue distribution of immunoglobulin coated superparamagnetic iron-oxide nanoparticles. PLoS ONE, 4(2):e4343 2009. PMID 19183814
- Kadiu I, Wang T, Schlautman JD, Dubrovsky L, Ciborowski P, Bukrinsky M, Gendelman HE. HIV-1 transforms the monocyte plasma membrane proteome. Cell Immunol., 258(1):44-58 2009. PMID 19358982
- Reynolds AD, Stone DK, Mosley RL, Gendelman HE. Nitrated alpha synuclein induced alterations in microglial immunity is regulated by CD4+ T cell subsets, J. Immunol., 182(7):4137-49 2009. PMID 19299711
- Liu J, Gong N, Huang X, Reynolds AD, Mosley RL, Gendelman HE. Neuromodulatory activities of CD4+CD25+ regulatory T cells in a murine model of HIV-1 associated neurodegeneration. J. Immunol. 15;182(6):3855-65 2009 PMID 19265165
- Schifitto G, Zhong J, Gill D, Peterson DR, Gaugh MD, Zhu T, Tivarus M, Cruttenden K, Maggirwar SB, Gendelman HE, Dewhurst, S, Gelbard HA. Lithium therapy for HIV-1 associated neurocognitive impairment. J. Neurovirol. 52(2);176-186 2009. PMID 19306230
- Kiyota T, Yamamoto M, Schroder B, Jacobsen MT, Swan RJ, Lambert MP, Klein WL, Gendelman HE, Ransohoff RM, Ikezu T. AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. Molecular Ther 17 (5):803-9 2009. PMID 19277012
- Nowacek A and Gendelman HE. NanoART, neuroAIDS and CNS drug delivery. Nanomedicine, Jul;4(5):557-74 2009. PMID 19572821
- Reynolds AD, Stone, DK, Mosley RL, Gendelman, H.E. Proteomic studies of nitrated alpha-synuclein microglia regulation by CD4+CD25+ T cells. J. Proteome Res. 8(7):3497-511 2009. PMID 19432400
- Huang X, Reynold AD, Mosley RL, Gendelman HE. CD4+ T cells in the pathobiology of neurodegenerative disorders. J. Neuroimmunol., 25;211(1-2):3-152009. PMID 19439368
- Eggert D, Dash PK, Serradji N, Dong C-Z, Clayette P, Heymans F, Dou H, Gorantla S, Gelbard HA, Poluektova L, and Gendelman HE. Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders. J. Neuroimmunol. 213:47-59 2009. PMID 19541372
- Nowacek A, Kosloski LM, Gendelman HE. Neurodegenerative disorders and nanoformulated drug development. Nanomedicine Jul;4(5):541-55 2009 PMID 19572820
- Gendelman HE. Preface. Lentiviruses and macrophages: Molecular and Cellular Interactions Eds. Moira Desport, 2009.
- Keblesh JP, Dou H, Gendelman HE, Xiong H. 4-Aminopyridine improves spatial memory in a murine model of HIV-1 encephalitis. J. Neuroimmune Pharmacol. Sep;4(3):317-27 2009. PMID 19462247
- Joseph J, Clifford D, Douglas SD, Fox H, Gendelman HE, Gonzalez-Scarano F, Grant I, Major E, McArthur J, the NeuroAIDS research participants. Planning Future Strategies for Domestic and International NeuroAIDS Research, July 24-25, 2008 J. Neuroimmune Pharmacol. 4(3):283-972009. PMID 19455426
- Kiyota T, Yamamoto M, Xiong H, Lambert MP, Klein WL, Gendelman HE, Ransohoff RM, Ikezu, T. CCL2 accelerates microglia-mediated Abeta oligomer formation and progression of neurocognitive dysfunction. PLoS One. Jul10;4(7);e6197 2009. PMID 19593388
- Stone DK, Reynolds AD, Mosley RL, Gendelman HE. Innate and adaptive immunity for the pathobiology of Parkinson's disease. Antiox. Redox. Signaling Sep;11(9):2151-66 2009. PMID 19243239
- Liu Y, Uberti M, Mosley RL, Gendelman HE, Boska M. An Image Warping Technique for Rodent Brain MRI-Histology Registration Based On Thin-Plate Splines with Landmark Optimization. Proc. SPIE Med. Imaging 2009
- Uberti M, Liu Y, Dou H, Mosley RL, Gendelman HE, Boska M. Registration of in vivo MR to histology of rodent brains using blockface imaging. In press, Proc. SPIE Med. Imaging 2009
Additional publications in pubmed.gov
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Dr. Gendelman's biographical information
Visit Dr. Gendelman's laboratory